1. Field of the Invention
This invention relates to a method for the use of a lignan complex isolated from flaxseed for the treatment of atherosclerosis, e.g. reducing or preventing the development of hypercholesterolemic atherosclerosis, for reducing total cholesterol and for raising HDL-C in blood.
2. Description of the Prior Art
Hypercholesterolemia is a major risk factor for atherosclerosis (narrowing of the artery due to deposition of fat in the arterial wall) and related occlusive vascular diseases such as heart attack, stroke and other peripheral vascular diseases. Heart disease is the number one killer. Hypercholesterolemic atherosclerosis has been reported to be associated with oxidative stress increase in levels of reactive oxygen species (ROS), production of ROS by polymorphonuclear leukocytes as assessed by chemiluminescence (PMNL-CL), and a decrease in the antioxidant reserve. Pretreatment with antioxidants (vitamin E, probucol, garlic, purpurogallin, secoisolariciresinol diglucoside) reverses the effects of hypercholesterolemia. Flaxseed which is a rich source of xcex1-linolenic acid and richest source of plant lignans has been shown to be effective in reducing hypercholesterolemic atherosclerosis without lowering serum levels of cholesterol. Using flaxseed which has very low xcex1-linolenic acid, has shown that antiatherogenic activity of flaxseed is not due to xcex1-linolenic acid but may be due to lignan component of flaxmeal.
Presently the treatment of hypercholesterolemia and hypercholesterolemic atherosclerosis is to reduce hypercholesterolemia by using various lipid lowering agents such as bile acid sequestrant (cholestyramine, colestipol), nicotinic acid, HMG-CoA reductase inhibitor (lovastatin, provastatin, simvastatin, fluvastatin and atrovastatin) and gemfibrozil. Recently probucol which has both antioxidant and lipid lowering activity and vitamin E which has antioxidant activity have been used to prevent atherosclerosis and restenosis.
Drugs used for lowering serum lipids and for treatment of atherosclerosis (heart attack and stroke) have many side effects and are expensive. Fibric acid derivatives (gemfibrozil) produces gall stones, myopathy and hepatomegaly. Nicotinic acid produces gastrointestinal symptoms, flushing, hyperglycemia, hepatic dysfunction, elevated uric acid, abnormal glucose tolerance, and skin rash. Bile acid sequestrant (cholestyramine, colestipol) produces gastrointestinal symptoms, and high serum levels of very low density-lipoprotein (VLDL). HMG-CoA reductase inhibitors (statin) produce gastrointestinal symptoms, myopathy and hepatotoxicity. Probucol produces diarrhea and decreases the serum levels of HDL (good cholesterol).
Prasad, U.S. Pat. No. 5,846,944, describes the use of secoisolariciresinol diglucoside (SDG), isolated from flaxseed, for reducing hypercholesterolemic atheroscleorsis and reducing serum cholesterol. However, isolating SDG from flaxseed is a relatively expensive procedure.
In Westcott et al., U.S. Pat. No. 6,264,853, a new lignan complex is described which has been isolated from flaxseed. This lignan complex typically contains SDG (35%), cinnamic acid glycosides and hydroxymethyl glutaric acid. Only a simple procedure is required to isolate this lignan complex from flaxseed.
The purpose of the present invention is to provide a method of using the above lignan complex derived from flaxseed for medical purposes.
In accordance with this invention, it has been found that a lignan complex isolated from flaxseed can safely be administered to humans or non-human animals for the treatment of a variety of diseases. The complex and a method for its production are described in Westcott et al., U.S. Pat. No. 6,264,853, issued Jul. 24, 2001, and incorporated herein by reference. This complex is used in substantially pure form, e.g. a purity of at least 95%, and contains secoisolariciresinol diglucoside (SDG), cinnamic acid glucosides and hydroxymethyl glutaric acid. It typically has a nominal molecular weight in the range of about 30,000 to 100,000. The complex can be administered orally or intraperitoneally and has been found to be highly effective when administrated in a daily oral dosage of 20 to 60 mg per kg of body weight. The oral doses may conveniently be in the form of tablets or capsules and the complex may be used together with a variety of pharmaceutically acceptable diluents or carriers.
When administered to humans or non-human animals, the complex has been found to be highly effective for treating hypercholesterolemic atherosclerosis, as well as for reducing total cholesterol and raising HDL-C in blood. Thus, it is useful for the prevention and treatment of coronary artery disease, stroke and other peripheral vascular diseases.